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Skip to 0 minutes and 14 seconds Now, formulation and the dosage forms. There aren’t many of them. We have aqueous solution. We have powder for injection that is lyophilized powder. We have pellet for implantation, particularly for the hormones in the veterinary formulation. We can use a suspension for intramuscular(IM) injection or you can use emulsion or microemulsion for subcutaneous(SQ) injection. But for human use most of them come as the powder for injection or the aqueous solution, the prefilled syringe. Now one important procedure in the formulation and the manufacturing of biologics is the freeze-drying. So we are going to talk about Freeze-Drying process for the production biologics. So the Freeze-Drying process is used to prepare lyophilized powder for injection. The first step is or involves freezing.

Skip to 1 minute and 30 seconds That is to lower the temperature to the eutectic point to freeze the protein solution. And that is followed by primary drying which is where the temperature is lower further to minus 40 degrees centigrade. And then apply negative pressure to remove the crystallized water. And after that the secondary drying. The temperature is now raised from minus 40 to the eutectic temperature and then back to the room temperature. And this secondary drying is to remove water bound to protein or excipients. So let’s look at this graph that shows the freeze-drying cycle.

Skip to 2 minutes and 23 seconds There are two components or two condition of the free drying cycle: the temperature and the pressure

Skip to 2 minutes and 32 seconds Freezing: so the solution is lowered to the eutectic point. Here the primary drying, the temperature is lowered to minus 40 degrees centigrade. And that primary drying lasts for a certain period of time. So depending on the time of drying of the drying process. It may end up biologics with different kind of property. And the secondary drying. The temperature is raised to the eutectic temperature or point and then back to the room temperature.

Injectable Biologics

For now, most biologics are administered via the intravenous or subcutaneous route, both requiring the injectable dosage form. The increasing use of biologics has stimulated innovations in novel injectable drug delivery systems. The conventional intravenous formulation is not suitable for biologics delivery due to its high viscosity, higher dosage volume, higher molecule size, and protein stability. Therefore, the formulation development of injectable biologics must take into consideration of the afore-mentioned factors. Further, future product innovation will likely focus on self-injectors, wearable drug delivery and needle-free injectors.

Two commercially available biologic formulations are injectable liquid or powder for injection, while microemulsion, suspension (for vaccine) or pellet (for implant) are occasionally used. Powder for injection is prepared through a freeze-drying process, which is briefly described as follows: The first step is to lower the temperature to the eutectic point, to freeze the protein solution. This is followed by primary drying at -40°C to remove crystallized water. Lastly, the temperature is raised from -40°C to eutectic point, and then to ambient temperature, to effectively remove water bound to the protein or excipients. The freeze-drying process is crucial as the condition of temperature, pressure and cycling time affect not only the quality but safety (immunogenicity) of the lyophilized product.

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This video is from the free online course:

Pharmacotherapy: Understanding Biotechnology Products

Taipei Medical University